乙型肝炎病毒聚合酶（潜在的药物靶标）末端蛋白质域的分

StephenW

Molecular, Evolutionary, and Structural Analysis of the Terminal Protein Domain of Hepatitis B Virus Polymerase, a Potential Drug Target
Timothy S Buhlig  1 , Anastasia F Bowersox  2 , Daniel L Braun  2 , Desiree N Owsley  1 , Kortney D James  1 , Alfredo J Aranda  1 , Connor D Kendrick  1 , Nicole A Skalka  1 , Daniel N Clark  1
Affiliations
Affiliations

    1
    Microbiology Department, Weber State University, 1415 Edvalson St., Ogden, UT 84408, USA.
    2
    Biology Department, Lebanon Valley College, 101 N. College Ave., Annville, PA 17003, USA.

    PMID: 32455999 DOI: 10.3390/v12050570

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Abstract

Approximately 250 million people are living with chronic hepatitis B virus (HBV) infections, which claim nearly a million lives annually. The target of all current HBV drug therapies (except interferon) is the viral polymerase; specifically, the reverse transcriptase domain. Although no high-resolution structure exists for the HBV polymerase, several recent advances have helped to map its functions to specific domains. The terminal protein (TP) domain, unique to hepadnaviruses such as HBV, has been implicated in the binding and packaging of the viral RNA, as well as the initial priming of and downstream synthesis of viral DNA-all of which make the TP domain an attractive novel drug target. This review encompasses three types of analysis: sequence conservation analysis, secondary structure prediction, and the results from mutational studies. It is concluded that the TP domain of HBV polymerase is comprised of seven subdomains (three unstructured loops and four helical regions) and that all three loop subdomains and Helix 5 are the major determinants of HBV function within the TP domain. Further studies, such as modeling inhibitors of these critical TP subdomains, will advance the TP domain of HBV polymerase as a therapeutic drug target in the progression towards a cure.

Keywords: hepatitis B virus; protein priming; terminal protein.

StephenW

乙型肝炎病毒聚合酶（潜在的药物靶标）末端蛋白质域的分子，进化和结构分析
Timothy S Buhlig 1，Anastasia F Bowersox 2，Daniel L Braun 2，Desiree N Owsley 1，Kortney D James 1，Alfredo J Aranda 1，Connor D Kendrick 1，Nicole A Skalka 1，Daniel N Clark 1
隶属关系
隶属关系

    1个
    韦伯州立大学微生物系，美国奥格登市爱德华森街1415号，犹他州84408，美国。
    2
    黎巴嫩谷学院生物系，美国宾夕法尼亚州安维尔市N. College Ave. 101号，宾夕法尼亚州17003。

    PMID：32455999 DOI：10.3390 / v12050570

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抽象

大约有2.5亿人患有慢性乙型肝炎病毒（HBV）感染，每年夺去近一百万的生命。当前所有HBV药物疗法（干扰素除外）的靶标都是病毒聚合酶。具体而言，是逆转录酶结构域。尽管没有针对HBV聚合酶的高分辨率结构，但最近的一些进展有助于将其功能映射到特定结构域。 HBV等肝炎病毒特有的末端蛋白（TP）结构域与病毒RNA的结合和包装以及病毒DNA的初始引发和下游合成有关-所有这些都使TP结构域成为有吸引力的新型药物靶标。这篇综述包括三种类型的分析：序列保守性分析，二级结构预测和突变研究的结果。结论是，HBV聚合酶的TP结构域由七个亚结构域（三个非结构环和四个螺旋区域）组成，并且所有三个环亚结构域和Helix 5是TP域中HBV功能的主要决定因素。进一步的研究，例如对这些关键TP子域的抑制剂进行建模，将使HBV聚合酶的TP域作为治疗药物的靶标，朝着治愈的方向发展。

关键词：乙型肝炎病毒；蛋白质启动末端蛋白。

StephenW

https://www.mdpi.com/1999-4915/12/5/570